cyclic-gmp and Neurogenic-Inflammation

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that results from liver failure and is characterized by a wide range of symptoms such as alteration in the sleep-waking cycle, neuromuscular coordination, mood, and cognition. The deregulation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathway is thought to play an important role in the etiology and progression of neurodegenerative diseases, and several studies pointed that the cGMP signaling is impaired in patients with HE and experimental models of chronic hyperammonemia. This review aimed to briefly present the current knowledge of the cGMP signaling pathways in neuroinflammation, neurogenesis, and memory in hepatic encephalopathy and its potential therapeutic role.

Topics: Animals; Cognition; Cyclic GMP; Disease Models, Animal; Hepatic Encephalopathy; Humans; Memory; Mice; Neurogenic Inflammation; Signal Transduction

Calcitonin gene-related peptide (CGRP), is produced in dorsal root ganglia (DRG) neurons and released from primary afferent neurons to mediate hemodynamic effects and neurogenic inflammation. In this work, we determined whether lipopolysaccharide (LPS), an inflammatory stimulator, could trigger CGRP release from cultured DRG neurons and if so, which cellular signaling pathway was involved in this response. Cytoplasmic concentration of calcium ([Ca(2+)](i)) plays a key role in neurotransmitter release, therefore [Ca(2+)](i) was also determined in cultured DRG cells using fluo-3/AM. The results showed that LPS (0.1-10 microg/ml) evoked CGRP release in a time- and concentration-dependent manner from DRG neurons. LPS also increased [Ca(2+)](i) in a concentration-dependent manner. The protein kinase C (PKC) inhibitors, calphostin C 0.5 microM or RO-31-8220 0.1 microM, and the cAMP-dependent protein kinase (PKA) specific inhibitor RP-CAMPS 30 microM or nonspecific inhibitor H8 1 microM inhibited 1 microg/ml LPS-evoked CGRP release and [Ca(2+)](i) increase from DRG neurons. The cGMP-dependent protein kinase (PKG) inhibitor Rp-8-pCPT-cGMPS 30 microM did not block the LPS response. These data suggest that LPS may stimulate CGRP release and [Ca(2+)](i) elevation through PKC and PKA, but not PKG signaling pathway in DRG neurons of neonatal rats.

Topics: Animals; Animals, Newborn; Calcitonin Gene-Related Peptide; Calcium; Carcinogens; Cells, Cultured; Colforsin; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Ganglia, Spinal; Lipopolysaccharides; Male; Neurogenic Inflammation; Neurons, Afferent; Potassium; Protein Kinase C; Protein Kinases; Rats; Rats, Wistar; Signal Transduction; Tetradecanoylphorbol Acetate; Up-Regulation